Prediction of adverse perinatal outcome and the mean time until delivery in twin pregnancies with suspected pre-eclampsia using sFlt-1/PIGF ratio.

PURPOSE: An elevated soluble fms-like tyrosine kinase-1 (sFlt-1) / placental growth factor (PlGF) ratio is associated with adverse perinatal outcome (APO) and the mean time until delivery (MTUD) in singleton pregnancies complicated by pre-eclampsia (PE). Data on APO and MTUD prediction in twin pregnancies using sFlt-1/PlGF ratio are scarce. We evaluated the predictive value of the sFlt-1/PIGF ratio regarding APO and MTUD in twin pregnancies with suspected PE and/or HELLP syndrome. METHODS: This is a single center retrospective cohort study. All twin pregnancies with suspected PE/HELLP and determined sFlt-1/PIGF were included. Composite APO (CAPO) was defined as the presence of at least one of the following outcomes: respiratory distress syndrome (RDS), intubation, admission to neonatal intensive care unit (NICU) and arterial umbilical cord pH value < 7.10. Selective fetal growth restriction (s-FGR) was analyzed separately. RESULTS: For final analysis, 49 twin pregnancies were included. Median sFlt-1/PIGF ratio was not significantly different in patients with CAPO compared to those without (89.45 vs. 62.00, p = 0.669). MTUD was significantly negative correlated with sFlt-1/PIGF ratio (r = -0.409, p < 0.001). For the whole study cohort, ROC analysis revealed no predictive value for sFlt-1/PIGF and CAPO (AUC = 0.618, 95% CI: 0.387-0.849, p = 0.254). However, sFlt-1/PIGF ratio showed a predictive value for s-FGR (AUC = 0.755, 95% CI: 0.545-0.965, p = 0.032). CONCLUSION: In twin pregnancies with PE and/or HELLP, sFlt-1/PIGF ratio may be helpful for s-FGR prediction and decision-making regarding close monitoring of high-risk patients. However, further prospective studies are warranted to define the role of sFlt-1/PlGF ratio as outcome predictor in twin pregnancies.

Role of sFlt-1/PIGF ratio and uterine Doppler in pregnancies with chronic kidney disease suspected with Pre-eclampsia or HELLP syndrome.

PURPOSE: Pregnancies of women with chronic kidney disease (CKD) are at higher risk of experiencing adverse perinatal (APO) and maternal outcome (AMO). Mean uterine artery pulsatility index (mUtA-PI) as well as the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are helpful tools in diagnosing pre-eclampsia (PE) in women with CKD. The aim of the study was to evaluate the role of sFlt-1/PIGF ratio and mUtA-PI as predictors for APO, AMO, preterm delivery and decline of kidney function in CKD pregnancies. METHODS: A total of 28 CKD pregnancies with suspected PE/HELLP syndrome were retrospectively included, in whom both sFlt-1/PIGF and mUtA-PI were determined during the third trimester. APO was defined as fetal growth restriction, respiratory distress syndrome, intubation, admission to NICU, 5 min Apgar <7 and intracerebral hemorrhage. AMO was defined as the development of PE, HELLP syndrome or resistant hypertension. Decline of kidney function was defined as a 25% increase of creatinine level after delivery. RESULTS: Of all included women, eight (28.6%) developed a PE/HELLP syndrome. AMO (28.6%) and APO (32.1%) were frequently observed. ROC analyses revealed a predictive value for AMO and sFlt-1/PIGF or mUtA-PI. Neither sFlt-1/PIGF nor mUtA-PI could predict APO or decline of postnatal kidney function. mUtA-PI was a predictor for preterm delivery. CONCLUSION: Uterine Doppler and sFlt-1/PIGF are predictors of AMO in CKD pregnancies. Therefore, both markers might be helpful for an improved risk assessment. However, neither sFlt-1/PIGF nor mUtA-PI were able to predict a decline of postnatal kidney function or APO.

Role of sFlt-1/PlGF ratio and feto-maternal Doppler for the prediction of adverse perinatal outcome in late-onset pre-eclampsia.

PURPOSE: The sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio and uterine artery Doppler have shown to be helpful in the diagnosis of pre-eclampsia (PE). The predictive value of the cerebroplacental ratio (CPR) regarding adverse perinatal outcome (APO) in low-risk pregnancies is intensively discussed. We evaluated the extent to which sFlt-1/PlGF ratio and feto-maternal Doppler may be useful in predicting APO in singleton pregnancies complicated by late-onset PE and/or HELLP syndrome. METHODS: This is a retrospective study from 2010 to 2018 consisting of singleton pregnancies with confirmed diagnosis of late-onset (lo ≥ 34 weeks) PE/HELLP syndrome in which sFlt-1/PlGF ratio and feto-maternal Doppler (mUtA-PI: mean uterine artery pulsatility index and CPR) were determined. The ability of sFlt-1/PlGF ratio, mUtA-PI, CPR and their combination to predict APO or SGA was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 67 patients were included in the final analysis. Of these, sFlt-1/PlGF was > 110 (defining angiogenic lo PE) in 40.3% (27/67), mUtA-PI was above the 95th centile in 34.3% (23/67) patients and CPR was lower than the 5th centile in 10.4% (7/67). Abnormal sFlt-1/PlGF and mUtA-PI as well as CPR were associated with a lower birth weight (BW). Late-preterm birth (< 37 weeks) as well as postnatal diagnosis of small for gestational age (SGA: BW < 3rd centile) was significantly more often in angiogenic lo PE cases. Neither sFlt-1/PIGF nor CPR or mUtA-PI were APO predictors. Only for sFlt-1/PlGF, ROC analysis revealed a significant predictive value for postnatal SGA (AUC = 0.856, p = 0.001, 95% CI 0.75-0.97). There was no statistical added value of combined SGA predictors as compared to sFlt-1/PlGF alone. CONCLUSIONS: In patients with lo PE, adding sFlt-1/PlGF ratio to routine antepartum fetal surveillance may be useful to identify cases of postnatal SGA. However, further prospective studies are warranted to define the role of feto-maternal Doppler and sFlt-1/PlGF ratio as outcome predictors.

New Aspects in the Diagnosis and Therapy of Fetal Hypoplastic Left Heart Syndrome.

Fetal hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease with a lethal prognosis without postnatal therapeutic intervention or surgery. The aim of this article is to give a brief overview of new findings in the field of prenatal diagnosis and the therapy of HLHS. As cardiac output in HLHS children depends on the right ventricle (RV), prenatal assessment of fetal RV function is of interest to predict poor functional RV status before the RV becomes the systemic ventricle. Prenatal cardiac interventions such as fetal aortic valvuloplasty and non-invasive procedures such as maternal hyperoxygenation seem to be promising treatment options but will need to be evaluated with regard to long-term outcomes. Novel approaches such as stem cell therapy or neuroprotection provide important clues about the complexity of the disease. New aspects in diagnostics and therapy of HLHS show the potential of a targeted prenatal treatment planning. This could be used to optimize parental counseling as well as pre- and postnatal management of affected children.

[Maternal Tumor Disease as a Reason for Repeated Test Failure in Cell-Free DNA Screening]. / Mütterliches Malignom in der Schwangerschaft als Ursache eines wiederholten Testversagens im nicht-invasiven Pränataltest.

Noninvasive prenatal testing (NIPT) is a screening test for fetal chromosome disorders. Recent studies show an incidental detection of maternal malignancies in NIPT diagnostics, where the simultaneous presence of multiple aneuploidies is described as an NIPT "anomaly". In this case, the diagnosis of a maternal tumor disease was made due to a repeat NIPT failure (no call).

Myocardial function in fetuses with lower urinary tract obstruction: Is there a cardiac remodeling effect due to renal damage?

OBJECTIVES: Cardiac remodeling due to renal dysfunction may have an impact on myocardial function (MF) of fetuses with lower urinary tract obstruction (LUTO). The aim was to identify possible differences in MF in LUTO fetuses compared with healthy controls and to look for interactions between urine biochemistry and MF indices. METHODS: This is a cohort study consisting of 31 LUTO fetuses and 45 healthy controls. Subgroups were generated according to intrauterine therapy (group 1: LUTO after therapy, group 2: LUTO without therapy at the time of examination, and group 3: controls). MF indices were measured using pulsed wave tissue Doppler imaging and M-mode. Furthermore, results of fetal urine biochemistry were gathered retrospectively. RESULTS: Among other findings, right ventricular (RV) e'/a' ratio was lower in group 1 compared with group 3 (p = .050). According to gestational age (GA) level-dependent analysis, RV isovolumetric relaxation time was significantly longer in group 2 compared with group 1 and group 3 at GA level 1 (19 wk of gestation). A significant positive correlation between RV e'/a' ratio and ß-2-microglobulin as well as α-1-microglobulin and potassium could be observed. CONCLUSION: We observed differences in MF and an association between ventricular filling pattern and renal protein secretion in LUTO fetuses. This can be interpreted as a sign of intrauterine cardiac remodeling.

sFlt-1/PlGF ratio for the prediction of the time of delivery.

PURPOSE: The soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio has been shown to be a useful parameter for the diagnosis and prediction of preeclampsia (PE). An increased sFlt-1/PlGF ratio can be closely linked to the need to deliver. The aim of the study was to examine the mean time until delivery (MTUD) in pregnant women with a strongly increased sFlt-1/PlGF ratio. METHODS: From 2010 to 2018, the sFlt-1/PlGF ratio was determined in 995 singleton pregnancies with diagnosis or suspicion of PE/HELLP syndrome and/or intrauterine growth restriction (IUGR). MTUD of patients with a value above 655 in < 34 weeks of gestation (group 1: n = 13) and above 201 in ≥ 34 weeks of gestation (group 2: n = 15) was calculated. Patients with a value > 85 but < 655 in < 34 weeks of gestation (group 3: n = 70) and a value > 110 but < 201 (group 4: n = 44) in ≥ 34 weeks of gestation acted as controls. RESULTS: 28 pregnant women with severely elevated sFlt-1/PlGF ratio and 114 controls were included. In group 1, MTUD was longer compared to group 2 without reaching statistical significance (96.7 h ± 132.2 vs. 47.7 h ± 44, p = 0.222). In pregnancies < 34 weeks of gestation (early onset), MTUD was significantly longer in group 3 compared to group 1 (361 h ± 317.3 vs. 96.7 h ± 132.2, p < 0.001). In pregnancies ≥ 34 weeks of gestation (late onset), MTUD was significantly longer in group 4 compared to group 2 (123.6 h ± 139.2 vs. 47.7 h ± 44, p = 0.002). CONCLUSIONS: The sFlt-1/PlGF ratio is suitable for decision-making regarding close monitoring of high-risk patients and need for lung maturation. However, for planning of delivery itself further prospective interventional studies are required to define its role as outcome predictor.

Esophageal achalasia and pregnancy: own observations in 43 patients and a review of the literature.

INTRODUCTION: Little is known concerning the interaction of achalasia and pregnancy and about an optimal time and type for treatment. Achalatic women of our collective of patients with at least one pregnancy in their history resulting in confinement or miscarriage were invited for a structured interview. MATERIALS AND METHODS: 43 of 109 female patients were included. Questionnaire contained questions on symptoms, type of symptoms, whether patients could link a specific event with outbreak of disease. Date of primary diagnosis and individual therapies were double checked against our documentation as well as duration of complaints and kind of therapy. Patients were asked about their obstetric history, whether and how symptoms had changed, and during which pregnancy week symptoms have occurred. Temporal correlation of the diagnosis of achalasia and pregnancy was investigated. RESULTS: There was no relationship between pregnancy and onset of achalasia. Risk of subfertility, undernourishment, premature birth, or miscarriage does not seem to be increased in achalasia. Health condition often worsened significantly during pregnancy, mainly in the first trimester and particularly in the untreated patients. CONCLUSIONS: It is advisable to clarify the diagnosis if symptoms suspicious of an achalasia are present before a planned pregnancy. In case of manifest achalasia, surgical treatment should be performed before pregnancy and the improvement in the state of health should be anticipated, as, otherwise, a considerable deterioration of the symptoms during pregnancy may occur. Scientific impact of our observations is very limited and prospective clinical trials are required.

Short-Time Impact of Laser Ablation of Placental Anastomoses on Myocardial Function in Monochorionic Twins with Twin-to-Twin Transfusion Syndrome.

Purpose To evaluate pre- and post-procedure myocardial function in monochorionic twins with TTTS who underwent laser ablation of placental anastomoses using pulsed wave tissue Doppler imaging (pw TDI). Materials and Methods 20 monochorionic twin gestations with TTTS were included and underwent laser ablation at our center between 2011 and 2014. Prior to and after the intervention, cardiac function was assessed by measuring the mitral annular plane systolic excursion (MAPSE), the tricuspid annular plane systolic excursion (TAPSE), Tei index, isovolumetric contraction time (ICT), ejection time (ET), isovolumetric relaxation time (IRT) for the left ventricle in pulsed wave Doppler (pw D) ultrasound as well as ICT, ET, IRT and Tei index in pw TDI for the left and right ventricle. E-, A-, E´- and A´-wave peak velocity and the systolic downward motion (S´) were measured for both ventricles and the E/A, E/E´ and E´/A´ ratios were calculated. In a mean of 1.3 (SD 0.6) days after laser ablation, this measurement protocol was repeated. Results Pre-intervention recipients had longer ICT, ET and IRT in pw D and pw TDI compared to donors not reaching statistical significance for most parameters. Statistically significant were prolonged ICT in pw D (p 0.01) and ET (p 0.01) in pw TDI in recipients. In donor fetuses preoperative myocardial function did not differ significantly from postoperative myocardial function except in increased left ventricular ejection time of the left ventricle in pw TDI (p 0.04) and an increased E´/A´ratio (p 0.01). After laser coagulation, myocardial function was slightly altered in recipients as ICT and IRT shortened and Tei indices decreased but only reaching statistical significance in shortened IRTs in pw TDI for both ventricles. Conclusion Laser ablation of placental anastomoses in TTTS might influence myocardial function in the postoperative period. Shortened IRT intervals may reflect an improvement of diastolic function in recipients.

Prenatal diagnosis of functionally univentricular heart, associations and perinatal outcomes.

OBJECTIVE: Functionally univentricular hearts (UVHs) represent cardiac anomalies in which either the pulmonary or systemic circulation cannot be supported independently. The purpose of our study was to determine perinatal outcomes after prenatal diagnosis of functionally UVH. METHODS: We retrospectively evaluated patients who presented between 2008 and June 2015 in our centre and in prenatal practice praenatal.de in Cologne. We included double inlet left ventricle (DILV), tricuspid valve atresia (TA), pulmonary valve atresia and intact ventricular septum (PA:IVS), unbalanced atrioventricular septal defect (AVSD), heterotaxy, hypoplastic left heart syndrome (HLHS) and hypoplastic left heart complex (HLHC). RESULTS: Of initially 155 patients, 128 were liveborn (82.6%). Ten neonates (7.8%) were lost to follow-up, in three (2.5%) neonates, parents decided for compassionate care. Overall survival after prenatal diagnosis of functionally UVH was 67.1%, and 90.4% on an intention-to-treat basis. Survival after surgery reached 93.7%. The majority of deaths occurred within the group of dominant RV (10/74, 13.5%). High risk HLHS with restrictive foramen ovale was associated with the lowest survival rate (13/17, 76.5%) with significant difference compared to survival rate in dominant LV (40/41, 97.6%, p < 0.05). CONCLUSION: These results should be explained to parents to ensure informed decisions and counselling. © 2016 John Wiley & Sons, Ltd.